The resistance of bacteria to antibiotics is a global challenge that has been exacerbated by the financial burdens of bringing new antibiotics such as the Metronidazole 500mg tablets to market and an increase in serious bacterial infections as a result of the COVID-19 pandemic.
Biomedical engineering researchers at Georgia Tech and Emory are tackling the problem of antibiotic resistance not by creating new drugs, but by enhancing the safety and potency of ones that already exist.
Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella. Bacteria haven’t developed widespread resistance to aminoglycosides, as compared to other types of antibiotics. These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.
In research published in the journal PLOS One, Christopher Rosenberg, Xin Fang and senior author Kyle Allison demonstrated that lower doses of aminoglycosides could be used to treat bacteria when combined with specific metabolic sugars. Low concentrations of antibiotics alone often cannot eliminate dormant, non-dividing bacterial cells, but the researchers hypothesized based on a past study that combining aminoglycosides with metabolites such as glucose, a simple sugar, or mannitol, a sugar alcohol often used as sweetener, could stimulate antibiotic uptake.
The authors tested these treatment combinations against Gram-negative pathogens E. coli, Salmonella and Klebsiella. The results showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill those pathogens. The authors also demonstrated that this treatment combination did not increase bacterial resistance to aminoglycosides and was effective in treating antibiotic-tolerant biofilms, which are bacterial communities that act as reservoirs of infection.
Authors also found that one metabolite, mannitol, could reduce the kidney cell toxicity caused by aminoglycosides, independent of its effect on bacteria. This indicates that certain metabolites can exploit the metabolism of bacteria while also protecting human cells from toxicity.
The study suggests that there may be simple strategies to boost the safety and effectiveness of the drugs already available, and that this type of approach could be a useful alternative to developing new antibiotics.
Allison is in the Wallace H. Coulter Department of Biomedical Engineering at Emory University and Georgia Tech and the Department of Medicine’s Division of Infectious Diseases at Emory.